# Optimizing RNA nanoparticles size and shape for enhancing cancer targeting and treatment

> **NIH NIH U01** · OHIO STATE UNIVERSITY · 2020 · $506,986

## Abstract

PROJECT SUMMARY
 RNA nanotechnology has progressed rapidly during the past several years. This nanotechnology includes
the integration of multiple functional modules into one nanoparticle, of which the scaffolds, ligands,
therapeutics, and regulators can be composed mainly or exclusively of RNA. We have constructed RNA
nanoparticles of diverse size, shape, and stoichiometry displaying high chemical and thermodynamic stability
and demonstrated their ability to harbor different functional groups, such as siRNA, miRNA, ribozyme, drug,
and cancer targeting RNA aptamer. All functional modules retain their authentic folding and independent
functionalities for specific cell binding, gene silencing, and cancer targeting in vivo. Upon systemic injection in
tumor bearing mice, RNA nanoparticles bind to xenograft and metastatic tumors specifically and strongly with
little to no accumulation in healthy vital organs and tissues 3-4 hours post-administration. The RNA
nanoparticles are non-toxic and display favorable biodistribution and pharmacokinetic profiles.
 Our long-term goal is to promote RNA nanoparticles as a new generation of drug for the treatment of
cancers in the clinic. The short-term goal of this project is to characterize the behavior of RNA nanoparticles in
vitro and in vivo, with an aim to improve the efficiency for specific cell targeting, internalization and intracellular
trafficking, favorable biodistribution without entrapment in liver, endosome escape, and tumor regression.
These studies are based on three central hypotheses: (1) intracellular trafficking pathways and endosome
escape are critical for effective cancer therapy; (2) biodistribution and pharmacological profiles of RNA
nanoparticles are shape and size dependent; and, (3) immune responses elicited by RNA nanoparticles are
highly dependent on RNA sequence, chemical modifications, size, shape, and stoichiometry. To address our
goals, we will (1) systemically dissect the intracellular pathways taken by RNA nanoparticles and enhance
their endosome escape capabilities; (2) inspect the pharmacokinetics (PK); pharmacodynamics (PD); and
biodistribution of RNA nanoparticles with the goal of enhancing cancer targeting with minimal accumulation in
healthy organs; and, (3) evaluate the immune responses of RNA nanoparticles to minimize non-specific side
effects, as well as develop methods to stimulate the immune system by incorporating immuno-stimulatory
modules to RNA nanoparticles for cancer immunotherapy. Upon completion of these pre-clinical studies, we
will have identified several RNA nanoparticles with optimized shape, size, and stoichiometry displaying
favorable safety profiles and high therapeutic efficacy to comply with FDA Investigational New Drug guidelines
for initiating clinical trials.

## Key facts

- **NIH application ID:** 10006088
- **Project number:** 5U01CA207946-05
- **Recipient organization:** OHIO STATE UNIVERSITY
- **Principal Investigator:** WILLIAM E. CARSON
- **Activity code:** U01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $506,986
- **Award type:** 5
- **Project period:** 2016-09-26 → 2022-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10006088

## Citation

> US National Institutes of Health, RePORTER application 10006088, Optimizing RNA nanoparticles size and shape for enhancing cancer targeting and treatment (5U01CA207946-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10006088. Licensed CC0.

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